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Multiple Sclerosis (MS) Pathophysiology

Szerző: Qabas Al-Jobori

Cultivating Expert Learners

Szerző: Anakany Ramirez

Inflammation

Szerző: Gustas Dovainys

Rheumatoid Arthritis

Szerző: Anthony Traboulsi

Cytokines or other growth factors draw progenitor cells to site.

NT-3 will not encourage regeneration after myelin breakdown.

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Goal: Allow Glial Scar to be Growth-Permissive

Remyelenize Axons

Subtopic

RXR agonist 9 cis retinoic acid. (Jeffrey K Huang, Andrew A Jarjour)

Introduce Growth-Promoting Factors

Extracellular Matrix

A-Cell Product

•Resorbable acellular porcine xenograft

Oncomodulin

Polysialic Acid Neural Cell Adhesion Molecule

L-1

Intrathecally delivered NT-3, NGF, and GDNF can promote axonal regeneration across the dorsal root entry zone (Ramer et al., 2002; Ramer et al., 2000)

• Intrathecal NT-3, delivered at the time of injury, promoted an upregulation of the growth-associated protein GAP-43

• Regeneration of cholera toxin B-labeled sensory axons across the DREZ and deep into the dorsal horn.

• Appearance of ED-1 expressing phagocytes marked end of effective treatment period of NT-3

• If treated within treatment period, regeneration continued, but in grey matter, not white.

cAMP & NT-3 combination has been shown to allow regeneration past lesion site

Mitigate effects of glial scar molecules that inhibit neurological regeneration

Neurocan

Chondroitin Sulfate Proteoglycans

In vivo studies have revealed remarkable long-distance regeneration of adult axons though CNS white matter tracts after enzymatic treatment to digest these proteoglycan side chains (Steinmetz, et al., 2005)

Injured corticospinal fibers and uninjured serotonergic fibers increase sprouting after enzymatic treatment to remove sugar epitopes (Barritt et al., 2006)

Enzyme which degrades Chondroitin Sulfate Proteoglycan shows local efficacy in enhancing axonal growth. (Cafferty et al., 2007)

• Chondroitinaise ABC (ChABC) was enzyme used to degrade chondroitin sulfate proteoglycan

•Axonal regrowth in lesion but not below it

• No significant motor function recovery

• Sensory recovery

Removing or preventing the production of sugar epitopes on proteoglycan molecules allows for axonal regeneration. (Bradbury, et al., 2002; Grimpe and Silver, 2004; McKeon, et al., 1995; McKeon, et al., 1991; Steinmetz, et al., 2005)

Semaphorin 3

Versican

Tenascin

Brevican

Ephrin B-2

Slit proteins

Phosphacan

Stop Production of Molecules that (potentially) cause gliosis

Cytokines

CNTF

IL-6

IL-1

thrombin

endothelin-1

TNF-alpha